Method using enteric-coated etidronate for treating calcification, hypercalcaemia, and calcinosis of the brain and other organs

Abstract

Among other things, compositions, kits, and methods for epilepsy therapy using a process for treating calcinosis manifested in Neurocysticercosis, Tuberous Sclerosis Complex, and Sturge-Weber Syndrome; an automated platform for real-time diagnosis and treatment of calcinosis comprising a computer-implemented method for using predictive analytics for administering a novel drug, Kamini™, to human patients generated at least in part from information that has been accumulated automatically from on-line resources.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application claims the benefit of U.S. Provisional Patent Application No. 62 / 548,344, filed on Aug. 21, 2017, which is incorporated by reference herein in its entirety.NOTICE OF COPYRIGHTS, TRADEMARKS, AND TRADE DRESS[0002]A portion of the disclosure of this patent document contains material that is subject to copyright protection. This patent document may show and / or describe matter that is or may become trade dress of the owner(s). The copyright and trade dress owners have no objection to the facsimile reproduction by anyone of the patent disclosure as it appears in the Patent and Trademark Office patent files or records, but otherwise reserves all copyrights and trade dress rights whatsoever. Kamini™ is an enteric-coated disodium etidronate optimized by Zy Therapeutics, LLC for treating neurological calcifications and other disease-producing calcifications.TECHNICAL FIELD[0003]The present invention, fully described in the claims, r...

AI Technical Summary

Benefits of technology

[0011]In general, in one aspect, an oral drug comprised of a safe and effective pharmaceutically active bisphosphonate, and, means for effecting delayed release of the bisphosphonate in the lower gastrointestinal tract to provide delivery of the pharmaceutical composition to the lower gastrointestinal tract of the human subject, specifically the proximal jejunum, and pharmaceutically effective absorption of the bisphosphonate, substantially alleviating upper gastrointestinal tract irritation and damage.

[0029]There are at least three pieces of evidence that suggest calcified lesions play a role in epileptogenesis: (1) high prevalence of typical cerebral calcifications in patients with seizures or epilepsy in the absence of other etiologies; (2) a positive correlation between endemic populations with increased proportions of calcification and seizure activity; and (3) an increased risk of continued seizure activity due to single cysticercal granuloma that calcify.

[0039]The radiological hallmark of the syndrome is double-contoured curvilinear calcification following a gyral pattern, becoming radiologically recognizable later in childhood and involving most frequently the occipital and parietal area. Histologic studies have shown that calcification in Sturge-Weber Syndrome appears to be related to a combination of gliosis due to chronic anoxia and venous hypertension along with altered vascular permeability of the abnormal vessels overlying the involved cortex. Wu, et al., demonstrated a link between severely diminished white matter perfusion, the presence of marked cortical calcification, and a higher seizure burden in children with Sturge-Weber Syndrome. These findings lend further support to prevailing theories regarding the development of calcification in Sturge-Weber Syndrome. These calcifications grow over time and are associated with further neurological deterioration.

[0043]There is an unmet need to address the calcinosis associated with these diseases. One approach would be to use binders of free calcium to keep the calcium bound in stable hydroxyapatite form sealing the harmful deposits. Bisphosphonates like Kamini™ (disodium etidronate) are potent binders of free calcium in the body. Through calcium chelation, disodium etidronate can minimize the adverse effects of an over-supply of calcium in the body. However, chronic use of disodium etidronate and other bisphosphonates can break down the protective phospholipids layers in the esophagus and stomach and lead to ulceration, erosion, and perforation. The formulation of an enterically-coated disodium etidronate would allow the medicine to pass unaltered through the esophagus, stomach, and duodenum, then dissolve, and be absorbed in the proximal jejunum.

Problems solved by technology

Humans become infected with T. saginata when they consume beef which has not been adequately cooked.

Humans can also become infected with T. solium eggs by ingesting contaminated food or water (human cysticercosis) or as a result of poor hygiene.

When cysts develop in the brain, neurocysticercosis may result.

Symptoms include epilepsy, severe headache and blindness, and, if left untreated, it can be fatal.

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